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Citation and License

Genome Biology 2004, 5:R25
doi:

Published: 15 March 2004

Abstract

Background

Factors affecting the organization and spacing of functionally unrelated genes in
metazoan genomes are not well understood. Because of the vast size of a typical metazoan
genome compared to known regulatory and protein-coding regions, functional DNA is
generally considered to have a negligible impact on gene spacing and genome organization.
In particular, it has been impossible to estimate the global impact, if any, of regulatory
elements on genome architecture.

Results

To investigate this, we examined the relationship between regulatory complexity and
gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity, such that
the amount of noncoding DNA between a gene and its nearest neighbors correlates positively
with that gene's regulatory complexity. Genes with complex functions are flanked by
significantly more noncoding DNA than genes with simple or housekeeping functions.
Genes of low regulatory complexity are associated with approximately the same amount
of noncoding DNA in D. melanogaster and C. elegans, while loci of high regulatory complexity are significantly larger in the more complex
animal. Complex genes in C. elegans have larger 5' than 3' noncoding intervals, whereas those in D. melanogaster have roughly equivalent 5' and 3' noncoding intervals.

Conclusions

Intergenic distance, and hence genome architecture, is highly nonrandom. Rather, it
is shaped by regulatory information contained in noncoding DNA. Our findings suggest
that in compact genomes, the species-specific loss of nonfunctional DNA reveals a
landscape of regulatory information by leaving a profile of functional DNA in its
wake.